Label-free optical quantification of structural alterations in Alzheimer's disease.

Moosung Lee,Yong Jeong,Shinhwa Lee,Kyoohyun Kim,Eeksung Lee,Jaehwang Jung,Jonghee Yoon,Yongkeun Park,Hyeonseung Yu

doi:10.1038/srep31034

Abstract

We present a wide-field quantitative label-free imaging of mouse brain tissue slices with sub-micrometre resolution, employing holographic microscopy and an automated scanning platform. From the measured light field images, scattering coefficients and anisotropies are quantitatively retrieved by using the modified the scattering-phase theorem, which enables access to structural information about brain tissues. As a proof of principle, we demonstrate that these scattering parameters enable us to quantitatively address structural alteration in the brain tissues of mice with Alzheimer’s disease.

Highlights

Imaging brain tissues is an essential tool in neuroscience because understanding brain structure provides rich information about brain functions and alterations associated with diseases
Employing quantitative phase imaging (QPI) techniques equipped with a motorised stage, holographic images of mouse brain tissue slices are measured with sub-micrometre resolution
With high contrast and transverse resolution, the phase images quantify the refractive index (RI) of the tissue with respect to the mounting solution (RI = 1.355, see Methods) and show the general anatomical features in a brain and spatial variations at subcellular structure level, these being undistinguishable with bright-field imaging

Summary

Introduction

Imaging brain tissues is an essential tool in neuroscience because understanding brain structure provides rich information about brain functions and alterations associated with diseases. Optical coherence microscopy has been utilised for label-free histology of a brain tissue[4] They only provide limited qualitative information about tissue structures. Employing QPI techniques equipped with a motorised stage, holographic images (amplitude and phase delay maps) of mouse brain tissue slices are measured with sub-micrometre resolution. This allows us to perform multi-scale imaging of a whole mouse brain tissue slice, which covers the sub-micrometre scale (subcellular organelles) to the millimetre scale (histological anatomy). Significantly modified, suggesting that the present approach provides a unique means to investigate pathophysiology of neurological disorders

Methods

Results

Conclusion